The immune system is incredibly complex, with numerous subsets of cells identified based on different characteristics, such as cell surface markers. Changes in immune cell populations occur with age, affecting the function and inflammation of the immune system. For example, T helper cells with the CD4 surface marker play a crucial role in immune protection throughout life, but undergo significant changes as individuals age. These changes include reduced levels of naive CD4+T cells, alterations in differentiation patterns, imbalances in cell ratios, and impaired functionality due to repeated antigenic stimulation and other factors. Understanding the nature of these changes in CD4+T cells and exploring ways to enhance their function is essential for improving the immune microenvironment in elderly individuals. Research should focus on mitochondrial dysfunction, metabolic changes, genetic and epigenetic factors, and other aspects to reverse immune aging. CD4+T cells not only influence other immune cell populations but also play a central role in orchestrating changes within the immune system.
CD4+T cells play a notable role in immune protection at different stages of life. As individuals age, significant alterations occur in the internal and external milieu of CD4+T cells. These changes encompass reduced naive CD4+T cell (CD4+TN) levels, thymic hypofunction, peripheral mechanism regulation, untimely quiescent withdrawal, and persistent environmental antigen stimulation. The interplay between the in vivo microenvironment and the aging immune system is intricately linked, resulting in a decline in effector CD4+ T cell (CD4+Teff) proliferation capacity, alterations in differentiation patterns, imbalances in the ratio of type 1 T helper cell (Th1) to type 2 T helper cell (Th2), changes in the ratio of type 17 T helper cells (Th17) to regulatory T cells (Treg), among others. Repeated antigenic stimulation, accelerated homeostasis, and delayed clearance lead to impaired mitochondrial respiration, reduced functionality, accumulation of memory subpopulations with autophagy deficits, loss of CD27 and CD28 surface molecule expression, increased production of cytotoxic molecules, and elevated levels of terminally differentiated CD4+T cells (CD4+TEMRA).
Enhancing the function of CD4+T cell phenotype and targeted depletion thereof represents a crucial approach for improving the immune microenvironment in elderly individuals. Future exploration can focus on the mitochondrial dysfunction, metabolic reprogramming, genetic and epigenetic changes, protein homeostasis imbalance, autophagy defects, loss of cellular plasticity, and reduction of T cell receptor (TCR) pool in aging CD4+T cells to clarify the nature of changes in different subtypes of CD4+T cells under immune aging. More attention should be paid to mutual influence and interaction in the process of CD4+T cell aging, which are necessary to reverse both multi-organ senescence and immune senescence. It is evident that CD4+T cells serve as the central hub, not only influencing other immune cell populations but also orchestrating changes within internal subsets and related signaling pathways.
